TY - JOUR
T1 - Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect
T2 - A secondary analysis of NRG CC001
AU - Cherng, Hua-Ren R
AU - Sun, Kai
AU - Bentzen, Søren
AU - Armstrong, Terri S
AU - Gondi, Vinai
AU - Brown, Paul D
AU - Mehta, Minesh
AU - Mishra, Mark V
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].
PY - 2024/4/3
Y1 - 2024/4/3
N2 - BACKGROUND: Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.METHODS: An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated.RESULTS: The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P = .03), whereas patients living < 4 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P = .03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR = 0.64, 95% CI: 0.48-0.85, P = .002) compared to those with highest MDASI-BT scores (HR = 1.24, 95% CI: 0.76-2.04, P = .39). Tumor histology also had a significant interaction (P = .01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR = 0.58, 95% CI: 0.43-0.77, P = .0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR = 1.15, 95% CI: 0.78-1.50, P = .48).CONCLUSIONS: Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.
AB - BACKGROUND: Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.METHODS: An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated.RESULTS: The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P = .03), whereas patients living < 4 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P = .03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR = 0.64, 95% CI: 0.48-0.85, P = .002) compared to those with highest MDASI-BT scores (HR = 1.24, 95% CI: 0.76-2.04, P = .39). Tumor histology also had a significant interaction (P = .01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR = 0.58, 95% CI: 0.43-0.77, P = .0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR = 1.15, 95% CI: 0.78-1.50, P = .48).CONCLUSIONS: Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.
KW - Humans
KW - Brain Neoplasms/radiotherapy
KW - Male
KW - Female
KW - Middle Aged
KW - Hippocampus/pathology
KW - Cranial Irradiation/methods
KW - Aged
KW - Memantine/therapeutic use
KW - Adult
KW - Follow-Up Studies
KW - Prognosis
U2 - 10.1093/neuonc/noad226
DO - 10.1093/neuonc/noad226
M3 - Article
C2 - 38069666
SN - 1522-8517
VL - 26
SP - 911
EP - 921
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 5
ER -